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Understanding Cytokines and Cell Communication

By: Michael Q. Pugliese and Peter T. Pugliese, MD
Posted: October 31, 2013, from the November 2013 issue of Skin Inc. magazine.
Understanding Cytokines and Cell Communication

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TGF-β is a protein that controls proliferation, cellular differentiation and other functions in most cells. It is a type of cytokine that plays a role in immunity, cancer, bronchial asthma, heart disease, diabetes and AIDS. TGF-β is secreted in at least three isoforms called TGF-β1, TGF-β2 and TGF-β3. TGF-β is part of a superfamily of proteins known as the TGF-β superfamily, which includes inhibins, activin, anti-müllerian hormone and bone morphogenetic protein. Most tissues have a high expression of TGF-β. Conversely, the anti-inflammatory cytokine IL-10 requires extracellular stimulation .

Some cells that secrete TGF-β also have receptors for TGF-β. This is known as autocrine signaling. Inflammatory stimuli that activate macrophages enhance the release of active TGF-β by promoting the activation of plasmin. Macrophages can also secrete endocytose IgG-bound latent TGF-β complexes that are secreted by plasma cells, and then release active TGF-β into the extracellular fluid.

All the functions of TGF-β are quite complex, but just remember that it is one of the good cytokines and performs important functions in the skin. It stimulates collagen and fibronectin synthesis. It is critical in cell chemotaxsis—the process of producing a chemical that attracts white cells to specific areas of the body—and it helps inhibit the breakdown of the intercellular matrix, which is a major factor in preventing the spread of cancer. Next, let’s examine a few of the interleukins produced by keratinocytes, starting with interleukin-1 and interleukin-3.

Interleukin 1 (IL-1)

IL-1 is a family of polypeptides, initially found to be produced by activated monocytes and macrophages that mediate a wide variety of cellular responses to injury and infection. Epidermal epithelial cells, keratinocytes, produce the epidermal, cell-derived thymocyte activating factor (ETAF), which has been recently shown to be identical to IL-1. The human epidermis is normally exposed to significant amounts of solar UV radiation. Human keratinocytes contain detectable amounts of IL-1 α and β mRNA and protein in the absence of apparent UV stimulation. Tissue culture studies of keratinocytes irradiated with UV light in the UVB range (290–320 nm) showed increased IL-1 activity by these cultures in vitro. The effect of UV irradiation on IL-1 represents a specific enhancement of IL-1 gene expression. Local increases of IL-1 may mediate the inflammation and vasodilation characteristic of acute UVB-injured skin. Systemic release of this epidermal IL-1 may account for fever, leukocytosis, and the acute phase response observed after excessive sun exposure.

You are probably familiar with the natural product azulene, which is a derivative of the chamomile plant. This is an effective anti-inflammatory agent that may inhibit IL-1 and NF-kB. In the category of new ingredients, Delisens, a hexapeptide by Lipotec, has been shown to inhibit IL-6 and IL-8, reducing inflammation. In a skin care formulation, it acts as an effective agent to ameliorate the discomfort of the nagging pain and itch occurring in sensitive skin.

Interleukin 3 (IL-3)